Time-dependent changes of inflammatory mediators in the lungs of humans exposed to 0.4 ppm ozone for 2 hr: A comparison of mediators found in bronchoalveolar lavage fluid 1 and 18 hr after exposure
Time-dependent changes of inflammatory mediators in the lungs of humans exposed to 0.4 ppm ozone for 2 hr: A comparison of mediators found in bronchoalveolar lavage fluid 1 and 18 hr after exposure
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DOI：
10.1006/taap.1996.0111
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发表时间：
1996-05-01
影响因子：
3.8
通讯作者：
Koren, HS
中科院分区：
文献类型：
--
作者：
Devlin, RB;McDonnell, WF;Koren, HS
人体急性暴露于臭氧会导致可逆性呼吸功能下降、细胞和生化变化，从而产生可介导炎症和急性肺损伤的物质。虽然暴露于臭氧后肺功能几乎立即下降，但尚不清楚人体中指示炎症的细胞和生化变化发生的速度有多快。支气管肺泡灌洗液（BAL）中性粒细胞（PMNs）和前列腺素（PGE(2)）水平升高，早在暴露后3小时，晚在暴露后18小时就有报道。本研究的目的是确定暴露后1小时内BAL液中的多种炎症介质是否升高。我们让8名健康志愿者两次接触：一次接触0.4 ppm的臭氧，一次接触过滤空气。每次暴露持续2小时，期间受试者进行间歇性剧烈运动（66升/分钟）。暴露后1小时行BAL。臭氧诱导PMNs、总蛋白、LDH、α -1抗胰蛋白酶、纤维连接蛋白、PGE(2)、血栓素B-2、C3a、组织因子和凝血因子VII迅速增加。此外，总细胞和肺泡巨噬细胞的恢复减少，肺泡巨噬细胞吞噬白色念珠菌的能力下降。将这些变化与一项早期研究中观察到的变化进行比较，该研究中受试者在相同暴露方案后18小时接受BAL治疗，结果表明，暴露后1小时IL-6和PGE(2)水平高于暴露后18小时，暴露后18小时纤维连接蛋白和组织纤溶酶原激活物水平较高，PMNs，蛋白质和C3a在两次暴露后基本相同水平。这些结果表明(i)暴露1小时后，几种炎症介质已经升高；（ii）一些介质在接触BAL液后的不同时间达到其最高水平。这些数据表明，炎症反应是复杂的，取决于一连串的时间事件，并且取决于感兴趣的介质，必须选择适当的采样时间。(C) 1996学术出版社，Inc.
Acute exposure of humans to ozone results in reversible respiratory function decrements and cellular and biochemical changes leading to the production of substances which can mediate inflammation and acute lung injury. While pulmonary function decrements occur almost immediately after ozone exposure, it is not known how quickly the cellular and biochemical changes indicative of inflammation occur in humans. Increased bronchoalveolar lavage (BAL) fluid levels of neutrophils (PMNs) and prostaglandins (PGE(2)) have been reported in humans as early as 3 hr and as late as 18 hr after exposure. The purpose of this study was to determine whether a broad range of inflammatory mediators are elevated in BAL fluid within 1 hr of exposure. We exposed eight healthy volunteers twice: once to 0.4 ppm ozone and once to filtered air. Each exposure lasted for 2 hr during which the subjects underwent intermittent heavy exercise (66 liters/min). BAL was performed 1 hr after the exposure. Ozone induced rapid increases in PMNs, total protein, LDH, alpha-1 antitrypsin, fibronectin, PGE(2), thromboxane B-2, C3a, tissue factor, and clotting factor VII. In addition, there was a decrease in the recovery of total cells and alveolar macrophages, and decreased ability of alveolar macrophages to phagocytize Candida albicans. A comparison of these changes with changes observed in an earlier study in which subjects underwent BAL 18 hr after an identical exposure regimen indicates that IL-6 and PGE(2) levels were higher 1 hr after exposure than 18 hr after exposure, fibronectin and tissue-plasminogen activator levels were higher 18 hr after exposure, and that PMNs, protein, and C3a were present at essentially the same levels at both times. These results indicate that (i) several inflammatory mediators are already elevated 1 hr after exposure; (ii) some mediators achieve their maximal levels in BAL fluid at different times following exposure. These data suggest that the inflammatory response is complex, depending on a cascade of timed events, and that depending on the mediator of interest one must choose an appropriate sampling time. (C) 1996 Academic Press, Inc.